Intravenous infusion is carried out for the purpose of supplying nutrients to maintain a patient's life when oral or nasal feeding is impossible or insufficient, when the digestion and absorption functions of the patient are in a poor state, even if such a feeding means can be carried out, or when the passage of food through the digestive tract makes the patient's condition or disease more serious. Examples of commercially available infusion preparations include a sugar intravenous infusion liquid which contains reducing sugars and the like, an amino acid intravenous infusion liquid which contains essential amino acids and the like, an electrolyte infusion liquid which contains minerals and the like, a fat emulsion which contains a plant oil emulsion and the like, and a vitamin mixture. These infusion preparations are appropriately selected depending on the condition of the patient and are mixed upon use. However, mixing these preparations at the time of their use requires complex handling and, above all things, raises the problem of microbial contamination. With the aim of overcoming such problems, various infusion preparations, in which some of the aforementioned infusion liquids are mixed in advance, have been proposed. Infusion preparations which contain sugars, amino acids, electrolytes and a fat emulsion, all being essential nutrients to be supplied, are especially useful from a clinical point of view.
However, since these sugar infusion liquids, amino acid infusion liquids, electrolyte infusion liquids and fat emulsion are different from one another in terms of the conditions for their stable existence, various problems arise when they are mixed, and the mixture becomes useless in many cases.
For example, because of its unstable nature, a fat emulsion is apt to form bulky fat particles and to cause phase separation (creaming) when mixed with other infusion liquids. In particular, divalent cations contained in an electrolyte infusion liquid cause aggregation and disintegration of fat emulsion particles.
In the case of an electrolyte infusion liquid, since it contains calcium and phosphoric acid as essential components to maintain the balance of electrolytes, it is apt to form calcium phosphate by the reaction of calcium with phosphoric acid and thereby to generate turbidity and precipitation. In order to prevent the formation of turbidity and precipitation, such an electrolyte infusion liquid is usually adjusted to a low pH value (less than pH 5). When such a electrolyte infusion liquid is mixed with an amino acid infusion liquid, the pH of the mixture increases to the amino acid pH value because of the strong buffer action of amino acids, thus requiring a large quantity of acidic materials (for example, hydrochloric acid, acetic acid and the like) to keep the pH value at a low level. However, acidic materials can be used only in a limited amount because a large quantity of acid spoils the balance of the infusion components. As a consequence, the pH value of the mixture of electrolyte and amino acid infusion liquids cannot be lowered to a satisfactory level, thus resulting in the generation of turbidity and precipitation during heat sterilization of the mixture.
In addition, when a mixture of an amino acid infusion liquid with a sugar infusion liquid is sterilized by heating, it is known that considerable coloring occurs due to the Maillard's reaction.
As described above, it is difficult to prepare a storable infusion preparation which contains a sugar, amino acids, electrolytes and a fat emulsion, in advance, because mixing these different types of infusion liquids or emulsions causes various problems such as precipitation, phase separation, denaturation, coloring and the like. Because of these problems, a fat emulsion, a sugar infusion liquid, an amino acid infusion liquid and an electrolyte infusion liquid are ordinarily mixed upon use. As a consequence, an alimentative infusion liquid has been desired which contains sugars, amino acids, electrolytes and a fat emulsion and can be stably stored.
There has been required a convenient method for complete alimentation via a peripheral vein in institutions where total intravenous alimentation is scarcely employed. Also, alimentation via a peripheral vein is a preferable method in order to completely feed a patient with temporary cut-off of oral alimentation for a short period of time. However, conventional alimentative infusion liquids to be administered via a peripheral vein have a low caloric value. For the total alimentation, it is therefore necessary to administer such an infusion liquid in an increased dose. However, an increase in the administration dose is accompanied by troubles such as angialgia and phlebitis, which restricts the administration dose. Thus, it is impossible to supply a sufficient energy to a patient, which makes the patient undernourished. Under such conditions, there is a risk that the patient suffers from unfavorable symptom. On the other hand, the injection of a common infusion liquid, which is to be administered via the main vein, into a peripheral vein causes side effects such as angialgia. Thus such an infusion liquid cannot be administered via a peripheral vein in practice.
Accordingly, it has been urgently required to develop a hyperalimentative infusion liquid which can be administered via a peripheral vein and enables total alimentation.
Under these circumstances, the present inventors have conducted extensive studies on an alimentative infusion liquid containing sugars, amino acids, electrolytes and a fat emulsion, which is stable and can be administered via a peripheral vein. As a result, they have successfully found out that an alimentative infusion liquid containing the above-mentioned components, which is free from various problems, for example, precipitation, phase separation, denaturation and coloring, and can be administered via peripheral vein without any trouble, can be obtained by improving the properties of each component, the composition and the liquid properties, thus completing the present invention. Accordingly, an object of the present invention is to provide an alimentative infusion liquid containing sugars, amino acids, electrolytes and a fat emulsion, which is hyperalimentative, excellent in stability and preservability and can be administered via a peripheral vein.